With respect to lipophilic drugs which are insoluble or practically insoluble in water, it is difficult to retain a sufficient blood concentration level thereof when they are administered orally because their absorbability is low. For this reason, administration of these drugs depends on oral mass administration or injection, which poses a major clinical problem and a great burden on patients. If the absorption speed, absorption rate and other factors of these drugs in oral administration are improved, treatment by oral administration will be possible and prior burdens on patients will be reduced; therefore, development of such an orally administrable preparation of a lipophilic drug which is insoluble or practically insoluble in water is urgently demanded by those skilled in the art.
For example, ubidecarenone, which is now clinically widely used as a pharmaceutical effective for improvement in coronary function, is well known to be low in absorbability upon oral administration because it is practically insoluble in water. When ubidecarenone is administered orally, its retention is transient in many tissues except for the tissues where ubidecarenone is liable to accumulate, such as the liver, spleen and adrenal; therefore, ubidecarenone needs to be administered in a large amount to ensure a sufficient level of pharmacological activity. In this case, frequent mass administration poses a great burden on the patients, even in oral administration, and is undesirable also from the viewpoint of prevention of adverse effects associated with mass administration.
With the recent progress of pharmaceutical preparation technology, this problem has been investigated from various viewpoints, including attempts to improve the absorbability of these lipophilic drugs by orally administering them after dissolution or emulsification dispersion using surfactants, oils and fats, or after such preparations. However, a satisfactory effect with such methods cannot always be obtained. Also, attention should be given to the use of surfactants and other additives from the viewpoint of safety. For example, nonionic surfactants such as polyoxyethylene hardening castor-oil and polyoxyethylene sorbitan monooleate have been used, but their pharmaceutical use in practical situations is often avoided since they pose problems such as hemolysis, mucosal irritation and mucosal deficiency.
On the other hand, safer synthetic surfactants such as fatty acid esters of polyglycerol and fatty acid esters of glycerol have recently been widely used; however, there are new demands for the development of natural type emulsifiers whose emulsifying capability is equivalent to, or higher than, that of the safer synthetic surfactants and whose overall safety are very high. Improvement in the absorbability of these lipophilic drugs by the use of any useful pharmaceutical additives will offer clinically significant utility.
As for bioactive peptides, the route of their administration has usually been limited to injection. This is because bioactive peptides in oral administration cannot be absorbed via the enteric canal due to the fact that most of them have a high molecular weight, and because their absorption into blood cannot be expected due to hydrolysis by proteolytic enzymes in the digestive tract. However, their administration by injection poses a great burden on patients. Under these conditions, various attempts have recently been made to develop orally administrable preparations of bioactive peptides, but there are no preparations which ensure good absorption into blood.
On the other hand, a recent report of the studies of drug delivery system suggests that the bovine milk fat globule membrane generally serves well as a very safe natural emulsifier [Drug Delivery System, 5 (2), 61-64, 1990]. The bovine milk fat globule membrane, known as a structural lipoprotein consisting mainly of lipid and protein, contains fat globules having a diameter of 0.1 to 10 .mu.m at the number of 3.6.times.10.sup.9 per ml of bovine milk on average. It is also known that these fat globules can maintain a stable emulsion state by the emulsive action of this bovine milk fat globule membrane. There are a large number of reports on biochemical studies of the structures and compositions of the bovine milk fat globule membrane. However, the grain size distribution of fat globules is rather wide; there are no reports on attempts to determine which grain size fraction is the most effective on the improvement of absorbability of lipophilic drugs and bioactive peptides when they are emulsified with the bovine milk fat globule membrane.